The object of these studies is to further characterize the factors which control the switch from fetal to adult hemoglobin synthesis in Man. Three closely related problems will be tackled: 1) To characterize the properties and genetic control of the F cell population. 2) To examine the possibility that the Hb F yields Hb A switch is under hormonal control using the chronically-catheterized fetal lamb model. 3) To try and develop an in vitro system for studying fetal globin gene expression. The long-term objective of these studies is the possibility of reversal of the Hb F yields Hb A switch as a therapeutic approach to sickle-cell anemia and Beta thalassemia.